Published in:
20-03-2024 | Hemophagocytic Lymphohistiocytosis | Original Article
Early hematopoietic cell transplantation for familial hemophagocytic lymphohistiocytosis in a regional treatment network in Japan
Authors:
Masataka Ishimura, Katsuhide Eguchi, Motoshi Sonoda, Tamami Tanaka, Akira Shiraishi, Yasunari Sakai, Takahiro Yasumi, Takayuki Miyamoto, Ilia Voskoboinik, Kunio Hashimoto, Shirou Matsumoto, Shuichi Ozono, Hiroshi Moritake, Hidetoshi Takada, Shouichi Ohga
Published in:
International Journal of Hematology
|
Issue 5/2024
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Abstract
Familial hemophagocytic lymphohistiocytosis (FHLH) is a fatal hyperinflammation syndrome arising from the genetic defect of perforin-mediated cytolysis. Curative hematopoietic cell transplantation (HCT) is needed before development of central nervous system (CNS) disease. We studied treatment outcomes of 13 patients (FHLH2 n = 11, FHLH3 n = 2) consecutively diagnosed from 2011 to 2022 by flow cytometric screening for non-myeloablative HCT in a regional treatment network in Kyushu, Japan. One patient with a novel PRF1 variant escaped screening, but all patients with FHLH2 reached diagnosis and 8 of them received HCT until 3 and 9 months of age, respectively. The earliest HCT was conducted 65 days after birth. Three pretransplant deaths occurred in newborns with liver failure at diagnosis. Ten posttransplant patients have remained disease-free, 7 of whom had no neurological involvement. Time from first etoposide infusion to HCT was shorter in patients without CNS disease or bleeding than in patients with those factors (median [range] days: 62 [50–81] vs. 122 [89–209], p = 0.016). Six of 9 unrelated patients had a PRF1 c.1090_1091delCT variant. These results suggest that the critical times to start etoposide and HCT are within 3 months after birth and during etoposide control, respectively. Newborn screening may increase the percentage of disease-free survivors without complications.